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Rationale: Sonographic septations are assumed to be important clinical predictors of outcome in pleural infection but the evidence for this is sparse. The inflammatory and fibrinolysis-associated intrapleural pathway(s) leading to septation formation have not been studied in a large cohort of pleural fluid (PF) samples with confirmed pleural infection, matched with ultrasound and clinical outcome data. Objectives: To assess the presence and severity of septations against baseline PF Plasminogen-Activator Inhibitor-1 (PAI-1) and other inflammatory and fibrinolysis-associated proteins as well as to correlate these with clinically important outcomes. Methods: We analysed 214 pleural fluid samples from the PILOT study, a prospective observational pleural infection study, for inflammatory and fibrinolysis-associated proteins using the Luminex platform. Multivariate regression analyses were utilised to assess association of pleural biological markers with septation presence and severity (on ultrasound), and clinical outcomes. Results: PF PAI-1 level was the only protein independently associated with septation presence (p=

Rationale: Patients with malignant/paramalignant pleural effusions (MPE/PMPEs) may have tunneled pleural catheter (TPC) management withheld due to infection concerns from immunosuppression associated with antineoplastic therapy. Objective: To determine the rate of infections related to TPC use and to determine the relationship to antineoplastic therapy, immune system competency and overall survival (OS)? Methods: We performed an international, multi-institutional study of MPE/PMPE patients undergoing TPC management from 2008-2016. Patients were stratified by whether or not they underwent antineoplastic therapy and/or were immunocompromised or not. Cumulative incidence functions and multivariable competing risk regression analyses were performed to identify independent predictors of TPC-related infection. Kaplan-Meier method and multivariable Cox proportional-hazards modeling were performed to examine for independent effects on OS. Results: A total of 1,408 TPCs were placed in 1,318 patients. Patients had a high frequency of overlap between antineoplastic therapy and an immunocompromised state (75-83%). No difference in the overall (6-7%), deep pleural (3-5%) or superficial (3-4%) TPC-related infection rates between subsets of patients stratified by antineoplastic therapy or immune status was observed. The median time to infection was 41 (interquartile range: 19-87) days following TPC insertion. Multivariable competing risk analyses demonstrated longer TPC duration was associated with a higher risk of TPC-related infection [subdistribution hazard ratio (95% CI): 1.03 (1.00-1.06), p=0.028]. Cox proportional-hazards analysis showed antineoplastic therapy was associated with better OS [hazard ratio (95% CI): 0.84 (0.73-0.97), p=0.015]. Conclusion: The risk of TPC-related infection does not appear to be increased by antineoplastic therapy use or an immunocompromised state. The overall rates of infection are low and comparable to immunocompetent patients with no relevant antineoplastic therapy. These results support TPC palliation for MPE/PMPE regardless of plans for antineoplastic therapy.

Background: Indwelling pleural catheters (IPC) are increasingly used for management of recurrent (especially malignant) effusions. Pleural infection associated with IPC use remains a concern. Intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) significantly reduces surgical referrals in non-IPC pleural infection, but data on its use in IPC-related pleural infection are scarce. Objective: To assess the safety and efficacy of intrapleural tPA and DNase in IPC-related pleural infection. Methods: Patients with IPC-related pleural infection who received intrapleural tPA/DNase in five Australian and UK centers were identified from prospective databases. Outcomes on feasibility of intrapleural tPA/DNase delivery, its efficacy and safety were recorded. Results: Thirty-nine IPC-related pleural infections (predominantly Staphylococcus aureus and gram-negative organisms) were treated in 38 patients; 87% had malignant effusions. In total, 195 doses (median 6 [IQR = 3–6]/patient) of tPA (2.5 mg–10 mg) and DNase (5 mg) were instilled. Most (94%) doses were delivered via IPCs using local protocols for non-IPC pleural infections. The mean volume of pleural fluid drained during the first 72 h of treatment was 3,073 (SD = 1,685) mL. Most (82%) patients were successfully treated and survived to hospital discharge without surgery; 7 required additional chest tubes or therapeutic aspiration. Three patients required thoracoscopic surgery. Pleurodesis developed post-infection in 23/32 of successfully treated patients. No major morbidity/mortality was associated with tPA/DNase. Four patients received blood transfusions; none had systemic or significant pleural bleeding. Conclusion: Treatment of IPC-related pleural infection with intrapleural tPA/DNase instillations via the IPC appears feasible and safe, usually without additional drainage procedures or surgery. Pleurodesis post-infection is common.

Objectives To evaluate the safety, effectiveness and cost-benefit of ambulatory pleural vent compared to conventional chest drain for pneumothorax following CT-guided biopsy of lung lesions (CTGB). Methods We retrospectively analysed electronic hospital records of patients requiring intervention for pneumothorax following CTGB. All patients treated with pleural vent over a 2-year period (August 2017–July 2019) were included and compared to a control group of all patients treated with chest drain over a previous 2-year period (August 2014–July 2016). Results Patients managed with a pleural vent had a shorter length of hospital stay compared to the chest drain group (median 0 days vs 4.5 days, p < 0.01). The mean cost of follow-up in the pleural vent group was £530.36 per patient compared to a mean of £2699.38 per patient in the chest drain group (p-value < 0.01). Conclusion Pleural vent can be a safe and effective alternative to conventional chest drain for the management of CTGB-related pneumothorax which allows patients to be managed on an outpatient basis with reduced hospital stays and lower associated healthcare costs. Advances in knowledge To the best of our knowledge, this is the first study demonstrating the safety and effectiveness of pleural vent for CTGB-related pneumothorax.

Background Pleurodesis is done as an in-patient procedure to control symptomatic recurrent malignant pleural effusion (MPE) and has a success rate of 75–80%. Thoracic ultrasonography has been shown in a small study to predict pleurodesis success early by demonstrating cessation of lung sliding (a normal sign seen in healthy patients, lung sliding indicates normal movement of the lung inside the thorax). We aimed to investigate whether the use of thoracic ultrasonography in pleurodesis pathways could shorten hospital stay in patients with MPE undergoing pleurodesis. Methods The Efficacy of Sonographic and Biological Pleurodesis Indicators of Malignant Pleural Effusion (SIMPLE) trial was an open-label, randomised controlled trial done in ten respiratory centres in the UK and one respiratory centre in the Netherlands. Adult patients (aged ≥18 years) with confirmed MPE who required talc pleurodesis via either a chest tube or as poudrage during medical thorascopy were eligible. Patients were randomly assigned (1:1) to thoracic ultrasonography-guided care or standard care via an online platform using a minimisation algorithm. In the intervention group, daily thoracic ultrasonography examination for lung sliding in nine regions was done to derive an adherence score: present (1 point), questionable (2 points), or absent (3 points), with a lowest possible score of 9 (preserved sliding) and a highest possible score of 27 (complete absence of sliding); the chest tube was removed if the score was more than 20. In the standard care group, tube removal was based on daily output volume (per British Thoracic Society Guidelines). The primary outcome was length of hospital stay, and secondary outcomes were pleurodesis failure at 3 months, time to tube removal, all-cause mortality, symptoms and quality-of-life scores, and cost-effectiveness of thoracic ultrasonography-guided care. All outcomes were assessed in the modified intention-to-treat population (patients with missing data excluded), and a non-inferiority analysis of pleurodesis failure was done in the per-protocol population. This trial was registered with ISRCTN, ISRCTN16441661. Findings Between Dec 31, 2015, and Dec 17, 2019, 778 patients were assessed for eligibility and 313 participants (165 [53%] male) were recruited and randomly assigned to thoracic ultrasonography-guided care (n=159) or standard care (n=154). In the modified intention-to-treat population, the median length of hospital stay was significantly shorter in the intervention group (2 days [IQR 2–4]) than in the standard care group (3 days [2–5]; difference 1 day [95% CI 1–1]; pInterpretation Thoracic ultrasonography-guided care for pleurodesis in patients with MPE results in shorter hospital stay (compared with the British Thoracic Society recommendation for pleurodesis) without reducing the success rate of the procedure at 3 months. The data support consideration of standard use of thoracic ultrasonography in patients undergoing MPE-related pleurodesis. Funding Marie Curie Cancer Care Committee

Pleural infection is a common condition encountered by respiratory physicians and thoracic surgeons alike. The European Respiratory Society (ERS) and European Society of Thoracic Surgeons (ESTS) established a multidisciplinary collaboration of clinicians with expertise in managing pleural infection with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified: 1) epidemiology of pleural infection, 2) optimal antibiotic strategy, 3) diagnostic parameters for chest tube drainage, 4) status of intrapleural therapies, 5) role of surgery and 6) current place of outcome prediction in management. The literature revealed that recently updated epidemiological data continue to show an overall upwards trend in incidence, but there is an urgent need for a more comprehensive characterisation of the burden of pleural infection in specific populations such as immunocompromised hosts. There is a sparsity of regular analyses and documentation of microbiological patterns at a local level to inform geographical variation, and ongoing research efforts are needed to improve antibiotic stewardship. The evidence remains in favour of a small-bore chest tube optimally placed under image guidance as an appropriate initial intervention for most cases of pleural infection. With a growing body of data suggesting delays to treatment are key contributors to poor outcomes, this suggests that earlier consideration of combination intrapleural enzyme therapy (IET) with concurrent surgical consultation should remain a priority. Since publication of the MIST-2 study, there has been considerable data supporting safety and efficacy of IET, but further studies are needed to optimise dosing using individualised biomarkers of treatment failure. Pending further prospective evaluation, the MIST-2 regimen remains the most evidence based. Several studies have externally validated the RAPID score, but it requires incorporating into prospective intervention studies prior to adopting into clinical practice.

Background Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to selected microbes. We designed a study with the aim to discover and investigate the total microbiome of pleural infection and assess the correlation between bacterial patterns and 1-year survival of patients. Methods We assessed 243 pleural fluid samples from the PILOT study, a prospective observational study on pleural infection, with 16S rRNA next generation sequencing. 20 pleural fluid samples from patients with pleural effusion due to a non-infectious cause and ten PCR-grade water samples were used as controls. Downstream analysis was done with the DADA2 pipeline. We applied multivariate Cox regression analyses to investigate the association between bacterial patterns and 1-year survival of patients with pleural infection. Findings Pleural infection was predominately polymicrobial (192 [79%] of 243 samples), with diverse bacterial frequencies observed in monomicrobial and polymicrobial disease and in both community-acquired and hospital-acquired infection. Mixed anaerobes and other Gram-negative bacteria predominated in community-acquired polymicrobial infection whereas Streptococcus pneumoniae prevailed in monomicrobial cases. The presence of anaerobes (hazard ratio 0·46, 95% CI 0·24–0·86, p=0·015) or bacteria of the Streptococcus anginosus group (0·43, 0·19–0·97, p=0·043) was associated with better patient survival, whereas the presence (5·80, 2·37–14·21, p Interpretation Pleural infection is a predominantly polymicrobial infection, explaining the requirement for broad spectrum antibiotic cover in most individuals. High mortality infection associated with S aureus and Enterobacteriaceae favours more aggressive, with a narrower spectrum, antibiotic strategies. Funding UK Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, Wellcome Trust, Oxfordshire Health Services Research Committee, Chinese Academy of Medical Sciences, and John Fell Fund.

Introduction and Aims. The first COVID-19 case in Malta was confirmed on the 7th of March 2020. This study is aimed at investigating a significant difference between the number of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) admissions and their inpatient outcome at Mater Dei Hospital during the COVID-19 pandemic when compared to the same period in 2019. Furthermore, we aim to determine predictors of mortality in AECOPD inpatients. Method. Data was collected retrospectively from electronic hospital records during the periods 1st March until 10th May in 2019 and 2020. Results. There was a marked decrease in AECOPD admissions in 2020, with a 54.2% drop in admissions (n = 119 in 2020 vs. n = 259 in 2019). There was no significant difference in patient demographics or medical comorbidities. In 2020, there was a significantly lower number of patients with AECOPD who received nebulised medications during admission (60.4% in 2020 vs. 84.9% in 2019; p ≤ 0:001). There were also significantly lower numbers of AECOPD patients admitted in 2020 who received controlled oxygen via venturi masks (69.0% in 2020 vs. 84.5% in 2019; p = 0:006). There was a significant increase in inpatient mortality in 2020 (19.3% [n = 23] and 8.4% [n = 22] for 2020 and 2019, respectively, p = 0:003). Year was found to be the best predictor of mortality outcome (p = 0:001). The lack of use of SABA pre-admission treatment (p = 0:002), active malignancy (p = 0:003), and increased length of hospital stay (p = 0:046) were also found to be predictors of mortality for AECOPD patients; however, these parameters were unchanged between 2019 and 2020 and therefore could not account for the increase in mortality. Conclusions. There was a decrease in the number of admissions with AECOPD in 2020 during the COVID-19 pandemic, when compared to 2019. The year 2020 proved to be a significant predictor for inpatient mortality, with a significant increase in mortality in 2020. The decrease in nebuliser and controlled oxygen treatment noted in the study period did not prove to be a significant predictor of mortality when corrected for other variables. Therefore, the difference in mortality cannot be explained with certainty in this retrospective cohort study., peer-reviewed

Objectives Recent observations indicate a potential survival benefit in patients with malignant pleural effusion (MPE) who achieve successful pleurodesis in comparison to patients who experience effusion recurrence post pleurodesis. This study aimed to explore this observation using two datasets of patients with MPE undergoing talc pleurodesis. Materials and Methods Dataset 1 comprised patients who underwent talc pleurodesis at Oxford Pleural Unit for MPE. Dataset 2 comprised patients enrolled in the TIME1 clinical trial. Pleurodesis success was defined as absence of need for further therapeutic procedures for MPE in the three months following pleurodesis. Data on various clinical, laboratory and radiological parameters were collected and survival was compared according to pleurodesis outcome (success vs. failure) after adjusting for the aforementioned parameters. Results Dataset 1 comprised 60 patients with mean age 74.1±10.3 years. The most common primary malignancies were mesothelioma, breast and lung cancer. 29 patients (48.3%) achieved pleurodesis. The adjusted odds ratio (aOR) for poor survival with pleurodesis failure was 2.85 (95% CI 1.08–7.50, =p 0.034). Dataset 2 comprised 259 patients from the TIME1 trial. The mean age was 70.8±10.3 and the most common primary malignancies were mesothelioma, lung and breast cancer. Pleurodesis was successful in 205 patients (79%). aOR for poor survival was 1.62 (95% CI 1.09–2.39, p = 0.015). Conclusion Achieving pleurodesis seems to impart a survival benefit in patients with MPE. Further studies are required to explore factors that may contribute to this phenomenon and to address the difference in survival between pleurodesis and indwelling pleural catheter interventions.

Malignant pleural effusions (MPE) are common and associated with disabling symptoms, and large hospitalisation costs [1]. Current management of recurrent MPE is symptomatic, with chest drain and talc pleurodesis, or indwelling pleural catheter (IPC) insertion. IPCs are an increasingly attractive option in patients wishing to avoid hospitalisation as they reduce initial length of stay [2, 3], but require repeated domiciliary drainage. Other patients opt for talc pleurodesis because, if successful, it represents a one-time definitive procedure, but it has a modest failure rate (20–30%) [4]. In the case of talc pleurodesis failure, IPC insertion is usually advocated with the consequence that a subset of patients with IPC in situ will have previously received ipsilateral intrapleural talc. IPCs are also increasingly being used in patients with recurrent benign pleural effusions (non-MPE) [5, 6]., Prior talc pleurodesis does not result in worsened outcomes from subsequent indwelling pleural catheter use, and patients should not be dissuaded from choosing talc as a primary treatment for recurrent pleural effusion. http://ow.ly/qAAC30mYmr3

Background Pleural infection (PI) is a common and complicated disease. Empirical antibiotic usage has been correlated to poor clinical outcomes. Although the identification of the pathogen is essential for successful treatment, conventional culture-based pathogen detection techniques fail in approximately 40% of cases. Therefore, the bacteriology of PI remains incomplete. Next generation sequencing (NGS) is a molecular-based methodology which could be applied to metagenomics studies and improve pathogen recognition. Aim To investigate and characterise the bacterial patterns of PI. Methods Pleural fluid specimens from the ‘Pleural Infection Longitudinal Outcome Study’1 (PILOT, n=243) were subjected to bacterial DNA extraction followed by 16S rRNA NGS. The DADA2 and Phyloseq R packages were used for the analysis of the data. Results We identified 363 distinct species of bacteria, with various abundances among the samples. Diverse patterns between monomicrobial and polymicrobial PI were detected. 131 (54%) samples had one pathogen with abundance over 50% and 89 (36%) samples had at least three pathogens with relative abundance over 10%, suggesting a polymicrobial infection. Discussion We developed a methodology to extract bacterial DNA from pleural fluid specimens derived from patients with PI and the quality was satisfactory to be used for NGS. 16S rRNA gene NGS has the potential to detect the total microbiome of pleural fluid samples1 from complex PI. Funding National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). Reference Corcoran, J.P., et al. Prospective validation of the RAPID clinical risk prediction score in adult patients with pleural infection: the PILOT study. Eur Respir J ( 2020).

Background Most patients with malignant pleural mesothelioma (MPM) seek treatment with malignant pleural effusion (MPE). In vitro evidence suggests that MPE may not be a simple bystander of malignancy, but rather potentially has biological properties that improve cancer cell survival and promote cancer progression. If this is the case, MPE management may need to shift from current symptomatic strategies to aggressive fluid removal to impact survival. Research Question Is there an association between pleural fluid exposure and survival in MPM? Study Design and Methods Data from 761 patients who received a diagnosis of MPM between 2008 and 2018 were collected from patient medical records in three UK pleural units. Data included factors previously identified as influencing prognosis in MPM. Medical imaging was reviewed for presence, size, and duration of pleural effusion. Time-dependent covariate analysis of pleural fluid exposure and survival (model included weight loss, serum albumin, hemoglobin, MPM subtype, performance status, chemotherapy, and age) and multivariate Cox regression analysis of pleurodesis and survival were conducted. Results Median overall survival was 278 days (interquartile range, 127-505 days; 95% CI, 253-301 days). Pleural fluid exposure duration showed no association with survival (hazard ratio, 1.0; 95% CI, 1.0-1.0). Median survival was 473, 378, and 258 days with complete, partial, and no pleurodesis (P = .008). Interpretation Pleurodesis success seems to be associated with improved survival; however, it is unclear whether duration of MPM exposure to pleural fluid is associated with survival within the limitations of this retrospective study. Future prospective studies are required to assess this potentially important mechanism.

Background: Pleural infection (PI) is a common and complex disease which can be life threatening for immunocompromised and elderly populations. Prior antibiotic use and special bacterial nutritional requirements hamper the accuracy of bacterial identification using current clinical culture-based techniques. Consequently, PI microbiology remains unclear. Next generation sequencing (NGS) has the potential to improve identification of the total bacterial population of a complex sample. Aim: To discover and characterise the microbial patterns of PI using NGS and bioinformatics techniques. Methods: Pleural fluid samples from the “Pleural Infection Longitudinal Outcome Study” (PILOT, ISRCTN50236700, n=243) underwent bacterial DNA extraction followed by 16S rRNA NGS using Illumina MiSeq. Data were analysed with DADA2 and Phyloseq R packages. Results: Analysis showed diverse microbiological patterns for PI as 391 different pathogens were identified up to the genus level. 131 (54%) samples had one pathogen with relative abundance over 50% and 89 (36%) samples had at least three pathogens with relative abundance over 10%, suggesting a polymicrobial infection. Streptococcus pneumoniae was detected in 40 (16%) and Staphylococcus aureus in 20 (8%) samples. Discussion: We established a methodology to extract bacterial DNA from patients with PI and used it as a template to apply NGS. 16S rRNA gene NGS provides a robust method to investigate the bacteriological patterns in pleural fluid of patients with PI. Funding: National Institute for Health Research, Oxford Biomedical Research Centre

Aim: To assess physical activity in patients with malignant pleural effusions(MPE) undergoing therapeutic interventions Background: There is no data to ascertain whether therapeutic interventions for MPE improve activity levels which are known to have a positive impact on various health related outcomes Methods: In this prospective cohort pilot study,patients undergoing a therapeutic intervention for MPE at the Oxford Pleural Unit were recruited between April 18-Nov 19. Patients with PS 4 or life expectancy Results: 20 patients were enrolled,complete data was available for 16 patients.11 patients underwent IPC insertion,3 had therapeutic aspiration and 2 had thoracoscopy+IPC for MPE management.Median volume of fluid drained was 1200 ml.Median VAS pre and post procedure was 43.5 mm(IQR 19-73) and 31 mm(IQR 19-42)respectively.The SWA was worn for a median of 2 days23hrs42 mins(on body awake time)and median % of time spent in activities worth ≥1.5 MET was 19.5% pre intervention.Post intervention,SWA was worn for a median of 2 days13hrs24mins(on body awake time) and median% of time spent in activities worth ≥1.5 MET was 13.14%.Median number of steps taken by patient pre and post intervention was 1603 and 659 respectively Conclusion: This study shows that pleural intervention didn9t have any impact on physical activity despite changes in VAS.

Malignant pleural mesothelioma(MPM) presents with malignant pleural effusion(MPE) in most patients. There is pre-clinical evidence that MPE may not be a simple bystander of malignancy,but potentially has biological properties increasing cancer cell proliferation.If this is the case,management of MPE may need to shift from current symptomatic strategies to aggressive fluid removal to impact on survival. Aim: to analyse the association of pleural fluid exposure(duration of effusion,& pleurodesis success)with survival in MPM. Method:Data on 761 patients diagnosed with MPM between 2008-2018 was collected from patients’ medical records in 3 UK pleural units.The medical images were reviewed for presence,size & duration of pleural effusion in order to analyse pleural fluid exposure(total number of days pleural effusion was present overall) & pleurodesis effects. Results: The median overall survival was 278 days(IQR 378).Median survival: 473,378,258 days (p 0.0006) with complete, partial,& no pleurodesis respectively.With time-dependent analysis,pleurodesis success remained a significant influencing factor on survival (p 0.002). There was no association between pleural fluid exposure time & survival (p 0.2) with time-dependent covariate analysis(model included serum albumin,MPM subtype,performance status,presence of symptoms at diagnosis,chemotherapy received). Conclusion: Pleurodesis success is associated with improved survival,however given the limitations of this retrospective study,it is unclear whether duration of MPM exposure to pleural fluid correlates with survival.Future prospective studies are required to assess this potentially important mechanism.

Background Solitary fibrous tumours of the pleura (SFTP), or pleural fibromas, are rare tumours that generally, but not universally, follow a benign course. Surgical resection is the standard treatment, but there are no evidence-based guidelines regarding the management of these tumours. Methods Five databases were searched from inception to April 1, 2019 for studies reporting on SFTP management. Results Twenty-seven studies met the inclusion criteria (1542 patients, all non-comparative case series); 98% of these patients underwent resection and all SFTP included were pathologically diagnosed. 394 out of 1299 cases (30.5%, 95% CI 27.8–32.8%) were malignant with recurrence rates of between 0% and 42.9%. A pleural effusion was always associated with a negative outcome, but no other features were consistently reported to have negative associations. Preoperative biopsies incorrectly reported malignant histology in two studies. Over 25% of cases of recurrence occurred when a complete (R0) resection had been achieved. The first recurrence occurred >5 years after the initial resection in at least 23% of cases. Conclusions There is strong evidence to support long-term surveillance after surgical resection of SFTP, even where a complete (R0) resection has been achieved; however, there is no clear evidence to inform clinicians regarding the selection of patients who should undergo resection. The rates of malignant SFTP and SFTP recurrence are higher than previously reported. Only those that were pathologically diagnosed or resected were included, which may bias the data towards more aggressive tumours. Data collection on radiologically diagnosed SFTP is required to draw conclusions regarding the timing and need for intervention., Long-term surveillance should be undertaken after a resection of solitary fibrous tumours of the pleura but further work is needed to determine which patients are likely to follow a malignant clinical course to decide timing and necessity of a resection https://bit.ly/2U10SaA

IntroductionThe rising incidence of pleural disease is seeing an international growth of pleural services, with physicians performing an ever-increasing volume of pleural interventions. These are frequently conducted at sites without immediate access to thoracic surgery or interventional radiology and serious complications such as pleural bleeding are likely to be under-reported.AimTo assess whether intercostal vessel screening can be performed by respiratory physicians at the time of pleural intervention, as an additional step that could potentially enhance safe practice.MethodsThis was a prospective, observational study of 596 ultrasound-guided pleural procedures conducted by respiratory physicians and trainees in a tertiary centre. Operators did not have additional formal radiology training. Intercostal vessel screening was performed using a low frequency probe and the colour Doppler feature.ResultsThe intercostal vessels were screened in 95% of procedures and the intercostal artery (ICA) was successfully identified in 53% of cases. Screening resulted in an overall site alteration rate of 16% in all procedures, which increased to 30% when the ICA was successfully identified. This resulted in procedure abandonment in 2% of cases due to absence of a suitable entry site. Intercostal vessel screening was shown to be of particular value in the context of image-guided pleural biopsy.ConclusionIntercostal vessel screening is a simple and potentially important additional step that can be performed by respiratory physicians at the time of pleural intervention without advanced ultrasound expertise. Whether the widespread use of this technique can improve safety requires further evaluation in a multi-centre setting with a robust prospective study.

ImportancePleural effusions frequently signal disseminated cancer. Diagnostic markers of pleural malignancy at presentation that would assess cancer risk and would streamline diagnostic decisions remain unidentified.ObjectiveThe present study aimed at identifying and validating predictors of malignant pleural effusion at patient presentation.DESIGN, SETTING, AND PARTICIPANTSA consecutive cohort of 323 patients with pleural effusion (PE) from different etiologies were recruited between 2013-2017 and was retrospectively analyzed. Data included history, chest X-ray, and blood/pleural fluid cell counts and biochemistry. Group comparison, receiver-operator characteristics, unsupervised hierarchical clustering, binary logistic regression, and random forests were used to develop the malignant pleural effusion detection (MAPED) score. MAPED was validated in an independent retrospective UK cohort (n= 238).Main Outcomes and MeasuresThe outcome was diagnostic of pleural effusion in patients, and the clinical and laboratory indicators available of the patient were measured.ResultsFive variables showed significant diagnostic power and were incorporated into the 5-point MAPED score. Age > 55 years, effusion size > 50% of the most affected lung field, pleural neutrophil count < 2,500/mm3, effusion protein > 3.5 g/dL, and effusion lactate dehydrogenase > 250 U/L, each scoring one point, predicted underlying cancer with the area under curve(AUC) = 0.819 (sensitivity=82%, specificity=74%,P< 10-15) in the derivation cohort. The AUC and net reclassification improvement (NRI) of MAPED score and cytology were not significantly different. However, the integrated discrimination improvement (IDI) of The MAPED score displayed a slight increment(PConclusionsThe MAPED score identifies malignant pleural effusions with satisfactory accuracy and can be used complementary to cytology to streamline diagnostic procedures.

IntroductionCurrent guidelines recommend an initial pleural aspiration in the investigation and management of suspected malignant pleural effusions (MPEs) with the aim of establishing a diagnosis, identifying non-expansile lung (NEL) and, at times, providing a therapeutic procedure. A wealth of research has been published since the guidelines suggesting that results and outcomes from an aspiration may not always provide sufficient information to guide management. It is important to establish the validity of these findings in a ‘real world’ population.MethodsA retrospective analysis was conducted of all patients who underwent pleural fluid (PF) sampling, in a single centre, over 3 years to determine the utility of the initial aspiration.ResultsA diagnosis of MPE was confirmed in 230/998 (23%) cases, a further 95/998 (9.5%) were presumed to represent MPE. Transudative biochemistry was found in 3% of cases of confirmed MPE. Positive PF cytology was only sufficient to guide management in 45/140 (32%) cases. Evidence of pleural thickening on CT was associated with both negative cytology (χ2 1df=26.27, p2 1df=10.39, p=0.001). In NEL 44.4% of patients did not require further procedures after pleurodesis compared with 72.7% of those with expansile lung (χ2 1df=5.49, p=0.019). In patients who required a combined diagnostic and therapeutic aspiration 106/113 (93.8%) required further pleural procedures.ConclusionsAn initial pleural aspiration does not achieve either definitive diagnosis or therapy in the majority of patients. A new pathway prioritising symptom management while reducing procedures should be considered.

Thoracic ultrasound is increasingly considered to be an essential tool for the pulmonologist. It is used in diverse clinical scenarios, including as an adjunct to clinical decision making for diagnosis, a real-time guide to procedures and a predictor or measurement of treatment response. The aim of this European Respiratory Society task force was to produce a statement on thoracic ultrasound for pulmonologists using thoracic ultrasound within the field of respiratory medicine. The multidisciplinary panel performed a review of the literature, addressing major areas of thoracic ultrasound practice and application. The selected major areas include equipment and technique, assessment of the chest wall, parietal pleura, pleural effusion, pneumothorax, interstitial syndrome, lung consolidation, diaphragm assessment, intervention guidance, training and the patient perspective. Despite the growing evidence supporting the use of thoracic ultrasound, the published literature still contains a paucity of data in some important fields. Key research questions for each of the major areas were identified, which serve to facilitate future multicentre collaborations and research to further consolidate an evidence-based use of thoracic ultrasound, for the benefit of the many patients being exposed to clinicians using thoracic ultrasound.

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.

Background Malignant pleural effusion (MPE) is common and imposes a significant burden on patients and health-care providers. Most patients require definitive treatment, usually drainage and chemical pleurodesis, to relieve symptoms and prevent fluid recurrence. Thoracic ultrasound (TUS) can identify the presence of pleural adhesions in other clinical scenarios, and could therefore have a role in predicting long-term pleurodesis success or failure in MPE. Methods Patients undergoing chest tube drainage and talc slurry pleurodesis for symptomatic MPE were recruited to a prospective observational cohort pilot study assessing whether TUS findings pre-talc and post-talc instillation predicted treatment outcome. Participants underwent TUS examination immediately before, and 24 h after talc slurry administration to derive pleural adherence scores for the affected hemithorax. The recorded TUS scans were additionally scored by two independent assessors blinded to the patient's clinical status. The primary outcome was pleurodesis success at 1-month and 3-month follow-up. Results Eighteen participants were recruited to the pilot study. Participants who suffered pleurodesis failure had a lower pleural adherence score at 24 h post-talc instillation than those who were successful (difference of 6.27; 95% CI, 3.94-8.59). TUS examination was acceptable to patients, while TUS scoring was highly consistent across all assessors (intraclass correlation coefficient, 0.762; 95% CI, 0.605-0.872). Conclusion A TUS-derived pleural adherence score may facilitate early prediction of long-term outcomes following chemical pleurodesis, with implications for personalized care and decision making in MPE. Further research is needed to evaluate this novel finding. Trial Registry ClinicalTrials.gov; No. NCT02625675; URL: www.clinicaltrials.gov.

Background: Indwelling pleural catheters (IPC) offer an alternative to talc pleurodesis in recurrent effusion, especially in patients wishing to avoid hospitalization. Two randomized trials have demonstrated reduced time in hospital using IPCs versus talc pleurodesis in malignant pleural effusion (MPE). However, the impact of IPCs on hospital services and patients has not been well studied. Objectives: To analyze long-term outcomes of IPCs and understand the hospital burden in terms of requirement for hospital visits and contacts with healthcare, while the IPC was in situ. Methods: IPC insertions in a tertiary pleural center were analyzed retrospectively. Reviews of patients with IPCs in situ considered “additional” to routine clinical follow-up were defined pre-hoc. Results: A total of 202 cases were analyzed: 89.6% MPE group (n = 181) and 10.4% non-MPE group (n = 21). There were a median 3.0 (interquartile range [IQR] 3) and 2.0 (IQR 2) ipsilateral pleural procedures prior to each IPC insertion in non-MPE and MPE groups, respectively (p = 0.26), and a mean 1.3 (SD 1.7) planned IPC-related outpatient follow-up visits per patient. There were 2 (9.5%) and 14 (7.7%) IPC-related infections in non-MPE and MPE groups, respectively. Four (19.0%) and 44 (24.3%) patients required additional IPC-related reviews in non-MPE and MPE groups, respectively (p = 0.6), and these occurred within 250 days post IPC insertion. Conclusions: Although IPCs decrease initial length of hospital stay compared to talc pleurodesis via chest drain, IPCs are associated with significant hospital-visit burden, in addition to planned visits and regular home IPC drainages. IPC-using services need to be prepared for this additional work to run an IPC service effectively.

Background and Objective: Chemical pleurodesis is performed for patients with MPE with a published success rate of around 80%. It has been postulated that inflammation is key in achieving successful pleural symphysis, as evidenced by higher amounts of pain or detected inflammatory response. Patients with mesothelioma are postulated to have a lower rate of successful pleurodesis due to lack of normal pleural tissue enabling an inflammatory response. Methods: The TIME1 trial data set, in which pleurodesis success and pain were co‐primary outcome measures, was used to address a number of these assumptions. Pain score, systemic inflammatory parameters as a marker of pleural inflammation and cancer type were analysed in relation to pleurodesis success. Results: In total, 285 patients were included with an overall success rate of 81.4%. There was a significantly higher rise in CRP in the Pleurodesis Success group compared with the Pleurodesis Failure group (mean difference: 19.2, 95% CI of the difference: 6.2–32.0, P = 0.004) but no significant change in WCC. There was no significant difference in pain scores or analgesia requirements between the groups. Patients with mesothelioma had a lower rate of pleurodesis success than non‐mesothelioma patients (73.3% vs 84.9%, χ2 = 5.1, P = 0.023). Conclusion: Change in CRP during pleurodesis is associated with successful pleurodesis but higher levels of pain are not associated. Patients with mesothelioma appear less likely to undergo successful pleurodesis than patients with other malignancies, but there is still a significant rise in systemic inflammatory markers. The mechanisms of these findings are unclear but warrant further investigation.

Summary Background The prevalence of malignant pleural effusion is increasing worldwide, but prognostic biomarkers to plan treatment and to understand the underlying mechanisms of disease progression remain unidentified. The PROMISE study was designed with the objectives to discover, validate, and prospectively assess biomarkers of survival and pleurodesis response in malignant pleural effusion and build a score that predicts survival. Methods In this multicohort study, we used five separate and independent datasets from randomised controlled trials to investigate potential biomarkers of survival and pleurodesis. Mass spectrometry-based discovery was used to investigate pleural fluid samples for differential protein expression in patients from the discovery group with different survival and pleurodesis outcomes. Clinical, radiological, and biological variables were entered into least absolute shrinkage and selection operator regression to build a model that predicts 3-month mortality. We evaluated the model using internal and external validation. Findings 17 biomarker candidates of survival and seven of pleurodesis were identified in the discovery dataset. Three independent datasets (n=502) were used for biomarker validation. All pleurodesis biomarkers failed, and gelsolin, macrophage migration inhibitory factor, versican, and tissue inhibitor of metalloproteinases 1 (TIMP1) emerged as accurate predictors of survival. Eight variables (haemoglobin, C-reactive protein, white blood cell count, Eastern Cooperative Oncology Group performance status, cancer type, pleural fluid TIMP1 concentrations, and previous chemotherapy or radiotherapy) were validated and used to develop a survival score. Internal validation with bootstrap resampling and external validation with 162 patients from two independent datasets showed good discrimination (C statistic values of 0·78 [95% CI 0·72–0·83] for internal validation and 0·89 [0·84–0·93] for external validation of the clinical PROMISE score). Interpretation To our knowledge, the PROMISE score is the first prospectively validated prognostic model for malignant pleural effusion that combines biological and clinical parameters to accurately estimate 3-month mortality. It is a robust, clinically relevant prognostic score that can be applied immediately, provide important information on patient prognosis, and guide the selection of appropriate management strategies. Funding European Respiratory Society, Medical Research Funding-University of Oxford, Slater & Gordon Research Fund, and Oxfordshire Health Services Research Committee Research Grants.

Malignant pleural effusion is a common complication of cancer and denotes a poor prognosis. It usually presents with dyspnea and a unilateral large pleural effusion. Thoracic computed tomography scans and ultrasound are helpful in distinguishing malignant from benign effusions. Pleural fluid cytology is diagnostic in about 60% of cases. In cytology-negative disease, pleural biopsies are helpful. Current management is palliative. Previously, first-line treatment for recurrent symptomatic malignant pleural effusion was chest drain insertion and talc pleurodesis, with indwelling pleural catheter insertion reserved for patients with trapped lung or failed talc pleurodesis. However, catheter insertion is an increasingly acceptable first-line treatment.

Introduction Malignant pleural effusion (MPE) signifies advanced disease and poor prognosis, with median survival ranging from 3 to 12 months. Pleural cytology is a widely used initial investigation for MPE but has a relatively low sensitivity of around 60%1. Negative pleural fluid cytology can result in a delay in diagnosis and treatment pathways. Negative CT findings alone cannot out malignancy. Pleural biopsy provides a definitive diagnosis of malignancy in the majority of cases of MPE,1 but is more invasive and may not be suitable for every patient. Objective The aim of this retrospective analysis was to assess the relationship between CT findings that are often associated with malignancy, and pleural cytology results. Methods We performed a retrospective analysis of all patients who had a pleural aspiration between 2015 and 2017 (n=219) with either positive pleural fluid cytology or a malignant pleural biopsy following negative cytology at a UK tertiary hospital. Patients were divided into two groups according to the cytology results. Chi-Square tests were used to analyse the relationship between CT findings and cytology result. Patients with negative pleural fluid cytology who did not go on to have a pleural biopsy were excluded. Results Of the 219 patients with diagnosed MPE, fluid cytology was positive in 151 (68.9%) patients. The remaining 68 (31.1%) patients had positive pleural biopsy as the initial cytology test was negative. Thoracic lymphadenopathy on CT was associated with positive pleural fluid cytology (odds ratio [OR]=1.82; p=0.042). Pleural nodularity (OR=4.76; p Conclusions This study suggests that pleural nodularity and pleural thickening on CT are associated with negative pleural fluid cytology. In patients with such features on CT and suspected MPE, a ‘straight to pleural biopsy’ approach should be considered. Reference Hooper C, Lee YCG, Maskell Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010.Thorax 2010;65:ii4-ii17.

Background Malignant pleural effusions (MPEs) are a sign of advanced malignant disease associated with high mortality and poor clinical outcome. Management of MPEs focuses on achieving symptomatic and radiological control of pleural fluid. Recent in vitro evidence has implicated the presence of even small volumes of pleural fluid in mesothelioma progression.1 This analysis investigated whether the presence of pleural fluid is associated with poorer survival in all MPE. Methods A review of all patients diagnosed with MPE between 2015–2017 was performed. Patients were grouped as either having achieved fluid control or not from initial radiological diagnosis until death. Kaplan Meier and Cox regression analysis was performed to assess the effect of a) achieving fluid control and b) duration of fluid, on patient survival. Results Analysis of the first 100 patients in our data set included 20 mesotheliomas, 27 breast, 4 gynaecological, 8 GI, 31 lung and 10 other cancers. 27 patients achieved fluid control before death and 70 did not. The group with fluid control comprised of those with IPC removal (3), successful pleurodesis (18) and resolution without pleurodesis (6), whereas the group without fluid control included those with ongoing IPC drainage (21), stable without intervention (2) and no resolution (47) at death. Three had no radiology after the initial aspiration and were thus excluded. Fluid control was associated with greater survival in Kaplan Meier survival curve analysis (p=0.009). Similarly, the Cox regression analysis demonstrated that successful control is associated with survival (p Conclusion Our findings suggest an association between pleural fluid control and greater survival. However, a statistically significant association was also found between time exposed to pleural fluid and greater survival. We cannot exclude the possibility of unknown confounders, and time dependant analysis may demonstrate different results. Further investigations with similar subgroups such as ‘ongoing IPC drainage vs. IPC removal’ may prove useful, and further analysis are ongoing. Reference Cheah HM, et al. Respirology 2017;22:192–199.

Introduction Diagnosing pleural infection can be challenging in the clinical setting. Positive microbiology is the gold standard, but pleural fluid culture requires days to establish and can be negative in 40% of patients with pleural infection. Rapid biomarker testing showing low pH, low glucose and very high LDH in pleural fluid is used to diagnose pleural infection in the correct clinical setting. Objectives To establish the diagnostic accuracy of low pH, low glucose and very high LDH in pleural fluid for pleural infection and establish the common alternative diagnoses leading to this biochemical pattern. Methods A retrospective analysis of pleural effusion results from a UK tertiary centre over a three year period. Pleural fluid results with either pH 1000 IU/L (total 173) were assessed to establish the frequency of non-infective final diagnoses and the relative specificity of each parameter calculated for the diagnosis of pleural infection. Results Of effusions with either a low pH, low glucose or LDH>1000 (n=173), the most common causes were infective 51% (n=89), with the most frequent alternative diagnosis malignant pleural effusion (MPE) 31% (n=53). Of note 10% (n=19) had co-existing malignancy and infection. The most common causative MPEs were lung 51%, mesothelioma 32% and breast 16%. In all pleural effusions with a pH 1000 (n=129), 47% were non infective in aetiology, 30% due to MPE. Table 1 illustrates further specific diagnoses within each cohort. Conclusions Pleural effusions with a low pH, low glucose or very high LDH often have a non-infective cause. While it may be appropriate to commence antimicrobial treatment, our results suggest that malignancy should be actively investigated. Pleural fluid pH

Background Pleural infection (PI) is a common and complicated disease, bearing a heavy healthcare burden worldwide. Definitive pathogen identification based on current methods occurs in only 40% of cases, mainly due to prior antibiotic administration and special bacterial nutritional culture requirements. To this end PI microbiology knowledge remains incomplete. Novel deep sequencing techniques could increase the rate of reliable pathogen identification and shed light on the complex polymicrobial patterns of PI. Aim To investigate and further characterise the microbial nature of PI using next generation sequencing (NGS). Methods Pleural fluid samples from the ‘Pleural Infection Longitudinal Outcome Study’ (PILOT, ISRCTN50236700, n=243) underwent bacterial DNA extraction followed by 16S rRNA NGS using Illumina MiSeq. Data were analysed with DADA2 and Phyloseq R packages. Results Bacterial DNA from pleural fluid samples was successfully extracted and sequenced. NGS detected 391 diverse pathogens up to the genus level and analysis showed that PI is a polymicrobial disease. 131 (54%) samples had one pathogen with relative abundance over 50% and 89 (36%) samples had at least 3 pathogens with relative abundance over 10%. Streptococcus Pneumoniae was detected in 40 (16%) and Staphylococcus Aureus in 20 (8%) samples. Discussion It is feasible to extract and sequence bacterial DNA from pleural fluid samples from patients with PI. 16S rRNA NGS is a robust method for investigating the total bacteriology of pleural fluid samples. Funding National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC).